COPD Aerosol Study Comparing the Efficacy of Nebulizers Versus Dry Powder Inhalers

• ClinicalTrials.gov Identifier: NCT02291016
• Recruitment Status: Completed
• First Posted: November 14, 2014
• Results First Posted: March 19, 2019
• Last Update Posted: March 19, 2019
• Sponsor: University of Tennessee Graduate School of Medicine
• Collaborator: Mylan Specialty L.P.
• Information provided by (Responsible Party): Rajiv Dhand, MD, University of Tennessee Graduate School of Medicine

Study Description

Brief Summary:

The purpose of this study is to compare drug delivery and lung function after treatment with formoterol from a nebulizer versus a dry powder inhaler (DPI) in patients recovering from severe exacerbations of COPD. This is to determine if one device is superior in providing better lung function and drug deposition in this clinical setting.

Condition or disease	Intervention/treatment	Phase
COPD Exacerbation	Drug: Formoterol; Other: Placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Dummy, Crossover, Single-Center Study Comparing the Efficacy of Nebulizers Versus Dry Powder Inhalers in the Treatment of Patients Recovering From Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
• Study Start Date: February 2015
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: March 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Formoterol via DPI then Formoterol via nebulizer; Group A: Received Formoterol 12 µg via DPI and placebo via nebulizer at treatment visit #1, and Formoterol 20 µg (solution form) via nebulizer and placebo via DPI at treatment visit 2. Placebo: The placebo used will be sterile, preservative free, normal saline for nebulizer inhalation and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Drug: Formoterol; Comparison of dosage administered via a nebulizer versus dosage administered via a dry powder inhaler. 12 µg Formoterol with the dry powder inhaler and 20 µg (solution form) of Formoterol with the nebulizer. Patients will receive formoterol and placebo at both study visit #1 and visit #2.; Other Names: Foradil; PERFOROMIST; Other: Placebo; Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.; Other Name: Normal Saline
Active Comparator: Formoterol via nebulizer then Formoterol via DPI; Group B: Received Formoterol 20 µg (solution form) via nebulizer and placebo via a DPI at treatment visit #1, and Formoterol 12 µg via a DPI with placebo via nebulizer at treatment visit 2. Placebo: The placebo used will be sterile, preservative free, normal saline for nebulizer inhalation and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Drug: Formoterol; Comparison of dosage administered via a nebulizer versus dosage administered via a dry powder inhaler. 12 µg Formoterol with the dry powder inhaler and 20 µg (solution form) of Formoterol with the nebulizer. Patients will receive formoterol and placebo at both study visit #1 and visit #2.; Other Names: Foradil; PERFOROMIST; Other: Placebo; Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.; Other Name: Normal Saline

Outcome Measures

Primary Outcome Measures :

1. The Difference Between the Values of Area Under the Response Curve for FEV1 [ Time Frame: Baseline through study completion (visit 1 through visit 2) ]
   The difference between the values of area under the response curve for FEV1 from baseline through four hours (AUC FEV1 0-4h) after inhalation of formoterol with a nebulizer or a dry powder inhaler.

Secondary Outcome Measures :

1. Percentage Change in Peak FEV1 From Baseline After Inhalation of Formoterol [ Time Frame: From pre-dose formoterol (baseline 0hrs) to 30 minutes, 1,2, and 4 hours post dose at visit 1 and measured again at visit 2 ]

   Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2.

   Steps:

   1. A baseline (pre-dose formoterol) FEV1 will be recorded.
   2. Subjects will be dosed with formoterol.
   3. Serial FEV1 assessments will completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so a peak measurement can be recorded.
   4. A percentage of change between the baseline and peak FEV1 will be recorded for this outcome measure. A higher value indicates a better result.
2. Absolute Increase in FEV1 From Baseline After Inhalation of Formoterol [ Time Frame: Measured at visit 1 and visit 2 after dosing and all FEV1 testing has been completed ]

   Increase in FEV1 from Baseline to 4 hours post dose of formoterol. This will be completed at visit 1 and visit 2.

   Steps:

   1. A baseline (pre-dose formoterol) FEV1 was recorded.
   2. Subjects was dosed with formoterol.
   3. Serial FEV1 assessments were completed, and recorded at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so serial FEV1 measurements could be recorded.
3. Peak FEV1 Between the Two Devices (Nebulizer and DPI) [ Time Frame: Measured from Start of visit 1 until the completion of visit 2 ]

   Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2.

   Steps:

   1. A baseline (pre-dose formoterol) FEV1 was recorded.
   2. Subjects were dosed with formoterol.
   3. Serial FEV1 assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so a peak measurement could recorded.

   5. Peak measurements from visit 1 and visit 2 will be compared for any significant change in FEV1 values.

4. Change in FEV1 as a Percentage of Predicted Normal After Inhalation of Formoterol [ Time Frame: Baseline through study completion (visit 1 through visit 2) ]

   Change in FEV1 from Baseline through 4 hours post formoterol dose. This was completed at visit 1 and visit 2.

   Steps:

   1. A baseline (pre-dose formoterol) FEV1 was recorded.
   2. Subjects were dosed with formoterol.
   3. Serial FEV1 assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FEV1 values were recorded.
   4. A percentage of change from baseline FEV1 to each serial measurement of FEV1 was collected. The % of change at each time point was then used to get a measure of overall percentage change of the predicted FEV1 value.
5. Area Under the Response Curve for FVC From Baseline Through Four Hours (AUC FVC0-4h) After Inhalation of Formoterol [ Time Frame: Measured at visit 1 and again at the end of visit 2 ]

   Steps:

   1. A baseline (pre-dose formoterol) FVC was recorded.
   2. Subjects were dosed with formoterol.
   3. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded.

   Data was all time points were used to obtain the total area under the curve

6. Percentage Change in Peak FVC From Baseline After Inhalation of Formoterol [ Time Frame: Measured at visit 1 and again at the end of visit 2 ]
   1. A baseline (pre-dose formoterol) FVC was recorded.
   2. Subjects were dosed with formoterol.
   3. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded.
   4. A percentage of change between the baseline and peak FVC will be recorded for this outcome measure.
7. Peak FVC Between the Two Devices (Nebulizer and DPI) [ Time Frame: Peak FVC at visit 1 will be compared to the peak FVC at visit 2 for any significant change. ]

   Steps:

   1. A baseline (pre-dose formoterol) FVC was recorded.
   2. Subjects were dosed with formoterol.
   3. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded.
   4. Peak FVC was recorded for this outcome measure and compared amongst groups.
8. Change in Dyspnea Based on the Borg Dyspnea Scale for Shortness of Breath (Pre-dose Administration and 60 Minutes After Inhalation of Formoterol With a Nebulizer or a DPI) [ Time Frame: Measured at visit 1 and again at the end of visit 2 ]
   The Shortness of Breath Modified Borg Dyspnea Scale The scale goes from 0-10, zero meaning no difficulty breathing and ten meaning maximal difficulty. A decrease of score indicates an improvement. Patients were asked to complete the scale pre-dose and again one hour post formoterol dose. This was completed at both visit 1 and visit 2. The value recorded was the difference between the baseline value and the post 60 minute value.

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Current or past cigarette smoking history of >/= 10 pack-years.
• FEV1/FVC ratio </= 70%.
• Known diagnosis of COPD.
• Current hospitalization for a primary diagnosis of acute exacerbation of COPD.
• Must be able to understand and willing to sign an informed consent document.

Exclusion Criteria:

• On a ventilator or mask ventilation.
• Allergy or contraindication to Formoterol use.
• Marked QTc prolongation (> 450 ms).
• Liver cirrhosis or chronic renal insufficiency (serum creatinine > 2 mg/dL).
• Atrial fibrillation with rapid ventricular response (heart rate > 110 bpm) or ventricular arrhythmia (frequent PVCs, ventricular tachycardia).
• Acute myocardial infarction within 12 weeks of patient study registration.
• Known pulmonary embolism.
• Known or suspected lung cancer.
• Known neuromuscular disease, stroke with residual hemiparesis, or untreated Parkinsonism
• Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm, or sub dermal implants).
• Inability to understand instructions.
• Participation in another investigational drug clinical trial within 30 days of patient study registration.

Contacts and Locations

Locations

United States, Tennessee

University of Tennessee Medical Center

Knoxville, Tennessee, United States, 37920

Sponsors and Collaborators

University of Tennessee Graduate School of Medicine

Mylan Specialty L.P.

Investigators

• Principal Investigator: Rajiv Dhand, MD; University of Tennessee Medical Center

More Information

• Responsible Party: Rajiv Dhand, MD, Principal Investigator, University of Tennessee Graduate School of Medicine
• ClinicalTrials.gov Identifier: NCT02291016
• Other Study ID Numbers: 3798
• First Posted: November 14, 2014
• Results First Posted: March 19, 2019
• Last Update Posted: March 19, 2019
• Last Verified: February 2019

Keywords provided by Rajiv Dhand, MD, University of Tennessee Graduate School of Medicine:

COPD; chronic obstructive pulmonary disease

Additional relevant MeSH terms:

Formoterol Fumarate; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action